6A16

Crystal structure of CYP90B1 in complex with uniconazole

6A16 の概要

• エントリーDOI: 10.2210/pdb6a16/pdb
• 分子名称: Cytochrome P450 90B1, PROTOPORPHYRIN IX CONTAINING FE, (1E,3S)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pent-1-en-3-ol, ... (6 entities in total)
• 機能のキーワード: cytochrome p450, phytohormone, brassinosteroid, uniconazole, oxidoreductase
• 由来する生物種: Arabidopsis thaliana (Mouse-ear cress)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57653.83

構造登録者

Fujiyama, K.,Hino, T.,Kanadani, M.,Mizutani, M.,Nagano, S. (登録日: 2018-06-06, 公開日: 2019-06-12, 最終更新日: 2024-03-27)

主引用文献

Fujiyama, K.,Hino, T.,Kanadani, M.,Watanabe, B.,Jae Lee, H.,Mizutani, M.,Nagano, S.
Structural insights into a key step of brassinosteroid biosynthesis and its inhibition.
Nat.Plants, 5:589-594, 2019

PubMed Abstract: Brassinosteroids (BRs) are essential plant steroid hormones that regulate plant growth and development. The most potent BR, brassinolide, is produced by addition of many oxygen atoms to campesterol by several cytochrome P450 monooxygenases (CYPs). CYP90B1 (also known as DWF4) catalyses the 22(S)-hydroxylation of campesterol and is the first and rate-limiting enzyme at the branch point of the biosynthetic pathway from sterols to BRs. Here we show the crystal structure of Arabidopsis thaliana CYP90B1 complexed with cholesterol as a substrate. The substrate-binding conformation explains the stereoselective introduction of a hydroxy group at the 22S position, facilitating hydrogen bonding of brassinolide with the BR receptor. We also determined the crystal structures of CYP90B1 complexed with uniconazole or brassinazole, which inhibit BR biosynthesis. The two inhibitors are structurally similar; however, their binding conformations are unexpectedly different. The shape and volume of the active site pocket varies depending on which inhibitor or substrate is bound. These crystal structures of plant CYPs that function as membrane-anchored enzymes and exhibit structural plasticity can inform design of novel inhibitors targeting plant membrane-bound CYPs, including those involved in BR biosynthesis, which could then be used as plant growth regulators and agrochemicals.

PubMed: 31182839
DOI: 10.1038/s41477-019-0436-6

実験手法

X-RAY DIFFRACTION (1.998 Å)